Regeneron Pharmaceuticals has announced encouraging initial data from an ongoing Phase 1/2/3 clinical trial of the Regeneron antibody cocktail, casirivimab and imdevimab, in hospitalized COVID-19 patients requiring low-flow oxygen. The analysis was prospectively designed to focus on patients who had not yet mounted their own immune response to SARS-CoV-2 (i.e., did not have antibodies at baseline: seronegative), as prior evidence suggested these patients were at greater risk. The primary clinical objective of this initial analysis was to determine if there was sufficient efficacy in these patients to warrant continuing the trial (i.e., futility analysis). The results passed the futility analysis (p<0.3 one-sided), as seronegative patients treated with the antibody cocktail had a lower risk of death or receiving mechanical ventilation (HR: 0.78; 80% CI: 0.51-1.2). The benefit was driven by results starting one-week post-treatment, when the risk of death or receiving mechanical ventilation was reduced by approximately half with antibody cocktail treatment, based on a post-hoc analysis.
Seronegative patients (n=217) had much higher viral loads than those who had already developed their own antibodies (seropositive) to SARS-CoV-2 at the time of randomization. In seronegative patients, the antibody cocktail reduced the time-weighted average daily viral load through day 7 by -0.54 log10 copies/mL, and through day 11 by -0.63 log10 copies/mL (nominal p=0.002 for combined doses). At day 5, the relative reduction compared to placebo was -1.1 log10 copies/mL (nominal p=0.002 for combined doses). As expected, in seropositive patients (n=270) the clinical and virologic benefit of the antibody cocktail was limited (clinical endpoint HR: 0.98; time-weighted average viral load reduction by day 7 of -0.20 log10 copies/mL for combined doses).
"These preliminary results in hospitalized patients, as well as data from the previously announced outpatient trial, indicate that antibodies produced by a patient's own immune response are important to control COVID-19 infection. In this trial, patients who had not yet mounted their own immune response had much higher viral loads and much worse clinical outcomes; for example in the placebo group, seronegative patients were almost three-times more likely to die compared to seropositive patients," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Moreover, the data from these trials in hospitalized and non-hospitalized patients suggest that Regeneron's antibody cocktail may compensate for an inadequate endogenous antibody response by reducing viral levels and the risk of adverse clinical outcomes. It is important to remember that while the virology results from this analysis of hospitalized patients were robust, the clinical efficacy data are based on a small data set of events and cannot be viewed as conclusive at this stage. A much larger trial will be required to rigorously characterize this effect and we believe the ongoing UK-based RECOVERY trial will provide those answers. It has already enrolled more than 2,000 hospitalized patients in the part of the trial evaluating adding the antibody cocktail to standard-of-care compared to standard-of-care alone."
The clinical and virological analyses include data from the Regeneron-sponsored trial evaluating hospitalized patients who were on low-flow oxygen (defined as maintaining oxygen saturation of >93% via nasal cannula, simple facemask, or similar device), including 217 who were seronegative when they entered the trial and 270 who were seropositive; although seronegative patients comprised less than half of the trial population, based on placebo rates they account for approximately two-thirds of the deaths in the absence of antibody cocktail treatment. Patients were randomized to receive the antibody cocktail (either 8,000 mg high dose or 2,400 mg low dose) or placebo, in addition to standard-of-care therapies, with 67% receiving remdesivir and 74% receiving systemic corticosteroids. Similar clinical and virologic efficacy was observed for the high and low doses of th...
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